ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.6136+1G>T

dbSNP: rs1593708662
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001779080 SCV000951930 likely pathogenic not provided 2024-06-14 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 44 of the POLE gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in POLE are known to be pathogenic (PMID: 23230001, 25948378, 30503519). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 655468). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
GeneDx RCV001779080 SCV002015737 uncertain significance not provided 2021-05-14 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); Canonical splice site variant with an unclear effect on protein function; Has not been previously published as pathogenic or benign to our knowledge

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